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Risk Assessment Metabolic Disorders by Prolonged Exposure to Low Doses of Benzene N.V

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Risk Assessment Metabolic Disorders by Prolonged Exposure to Low Doses of Benzene N.V Sys Rev Pharm 2020; 11(6): 420 424 A multifaceted review journal in the field of pharmacy E-ISSN 0976-2779 P-ISSN 0975-8453 Risk Assessment Metabolic Disorders by Prolonged Exposure to Low Doses of Benzene N.V. Sharapova1, S.I. Krasikov2, A.A. Petrova3, V.M. Boev4 1Candidate of biological Sciences, associate Professor of the Orenburg state medical University of the Ministry of Health of the Russian Federation, E-mail: [email protected] 2Doctor of medical Sciences, Professor of the Orenburg state medical University of the Ministry of Health of the Russian Federation, E-mail: [email protected] 3Assistant at the Orenburg state medical University of the Ministry of Health of the Russian Federation E-mail: [email protected] 4Doctor of medical Sciences, Professor of the Orenburg state medical University of the Ministry of Health of the Russian Federation, E-mail: [email protected] Article History: Submitted: 12.04.2020 Revised: 16.05.2020 Accepted: 21.06.2020 ABSTRACT Benzene is one of the most common environmental pollutants. functions under the influence of benzene. In addition, there was a However, the main attention of researchers is drawn to its decrease in the level of calcium, sodium and potassium in the blood carcinogenic and hematotoxic effect. The metabolic effects of this serum, which may reflect the effect of the pollutant on the processes hydrocarbon have been studied to a lesser extent and are mainly of reabsorption of electrolytes in the renal tubules on the one hand, related to high effects. The risks associated with the effect on the as well as on the regulation of electrolyte metabolism. In addition, body of non-toxic doses of this pollutant are practically not studied, under the influence of low doses of benzene in animals developed which was the purpose of the present study. insulin resistance (IR), estimated by glucose tolerance test (GTT). The Experiments lasting 7 weeks were carried out on animals that possible role of oxidative stress in the development of the described received drinking water containing benzene at a concentration of 10 disorders is discussed. µg/l, which is 1 maximum permissible concentration (MPC). Key words: benzene, rats, drinking water, maximum permissible It was shown that long-term consumption of water containing concentration, serum, total protein, uric acid, blood glucose, insulin benzene in concentration equal to 1 MPC in animals led to changes in resistance, enzymemia, dyslipoproteinemia biochemical parameters in blood serum, characterized by a decrease Correspondence: in the level of total protein and albumin, a moderate increase in the N. V. Sharapova activity of serum enzymes – alanine aminotransferase (ALAT), Candidate of Biological sciences, Associate Professor of the Orenburg aspartate aminotransferase (ASAT), alkaline phosphatase (ALP) and state medical university of the ministry of health of the Russian lactate dehydrogenase (LDH). Simultaneously, developed Federation hypercholesterolemia, triacylglycerolemia and dislipoproteinemia. In E-mail: [email protected] addition, there was a decrease in the concentration of urea and uric DOI: 10.31838/srp.2020.6.67 acid. The detected changes are considered as changes in liver @Advanced Scientific Research. All rights reserved INTRODUCTION not been studied enough, and the results obtained are According to the International Program on Chemical Safety ambiguous, which is the reason for this work [14, 15, 16]. (IPCS), benzene is one of the ten most hazardous substances for public health [1] and is one of the most common MATERIALS AND METHODS environmental pollutants [2]. At the same time, the vast The work was performed on 24 male rats of the Wistar line. majority of studies assess the negative impact of benzene on The weight of the animals at the beginning of the experiment human health in terms of its hemotoxicity and was 170 grams. The animals were kept in a vivarium, with carcinogenicity [3, 4], as there is more and more information day-night cycles of 12/12 hours. We used granulated food about the data on its toxicity to various organs and systems from Procorm (Novosibirsk, Russia) for feeding, balanced in in literature[5], rather than the carcinogenic effects of nutrients, vitamins and microelements. The animals were benzene. In particular, the toxicity of benzene in relation to given bottled water extracted from local artesian springs the cardiovascular system [6], its hypertensive effect «Akva vita» (LLC "Zhivaya Planeta", Orenburg, Russia) for associated with a violation of the formation of nitrogen oxide drinking. The amount of feed and water was not limited. [7] is shown. Administration of benzene to animals had a All experimental animals were divided into two equal groups hepatotoxic effect, which appeared by hepatospecific of equal weight and size. Animals of the first group served as hyperfermentemia [8], as well as nephrotoxic effect control group. Benzene was added to rats of the second group accompanied by depression of carbohydrate metabolism to a concentration of 0.01 mg / liter in drinking water, which enzymes in the cortical and cerebral substance of the kidneys corresponded to 1 maximum permissible concentration [9]. (MPC). The duration of the experiment was 8 weeks. An important manifestation of benzene toxicity can be Half of the animals from each group were tested for glucose observed when it acts on the human and animal body insulin tolerance (TSH) at the 6th week of the experiment. For this, resistance [10, 11, 12], as well as violations of the expression after 12 hours of starvation, but maintaining access to water, of fatty acid metabolism enzymes [13]. each rat was injected per os with a pipette 20% glucose It should be noted that, as a rule, observations related to both solution at the rate of 2 grams of dry matter per kg of mass. carcinogenic and non-carcinogenic effects of benzene relate Immediately before administration, and then every 30 to high doses of the toxicant, while the data available in minutes after administration of glucose, blood was collected literature indicate the need to study the effect on the body of from the tail vein of the animals, in which the glucose this aromatic hydrocarbon at low exposures. However, the concentration was determined using a glucose meter and test negative effects of benzene on the body in small doses have strips "Accu-Chek performa" (Roshe, Switzerland). 420 Systematic Review Pharmacy Vol 11, Issue 6, 2020 N. V. Sharapova et al / Risk Assessment Metabolic Disorders by Prolonged Exposure to Low Doses of Benzene All animals were removed from the experiment in Statistical processing was performed by using the "Microsoft compliance with ethical standards after 8 weeks. The blood Excel" package, the reliability of differences was evaluated by was collected in test tubes containing a coagulation activator the Student's test. of the company "Sarshted" (Germany) after decapitation and by centrifugation at 3000 rpm, the serum was separated from RESULTS the shaped elements. The results of the experiments are presented in table 1. Biochemical studies of blood serum were carried out at the From the data provided it follows that, in rats consumed "Cobas-6000" station of Roche (Switzerland) and included water containing benzene at a concentration of 1 MPC, there the determination of the level of total protein, albumin, was a decrease in the concentration of protein in the blood creatinine, uric acid, activity of aspartic and alanine serum by 7%, and the albumin content was lower by 10% than transaminases ALAT and ASAT, alkaline phosphatase in the control group. The urea content in the experimental (ALP), lactate dehydrogenase (LDH), the concentration of and control groups was within the normal range, but at the total cholesterol (TC) and its fractions high-density same time, it was lower in animals receiving benzene by 10%. lipoprotein cholesterol (HDL), lipoproteins very high low The level of serum creatinine in the groups did not differ, and and low density (VLDL and LDL), triacylglycerol (TAG), the uric acid in rats treated with benzene was 1.6 times lower ferritin, sodium, potassium, calcium, ferrum. than in intact ones. Table 1: Biochemical parameters of blood serum in rats with the use of water containing benzene (M ± m) Intact Benzene Indicators, units. P n=12 n=12 Total protein, g/l 63,0±1,2 58,9±0,56 P1-2= 0,0055 Albumin, g/l 35,8±0,86 32,4±0,33 P1-2= 0,0014 Urea, mmol/l 5,9±0,13 5,4±0,21 P1-2= 0,055 Creatinine, mmol/l 35,3±1,61 35,8±1,57 P1-2=0,826 Uric acid, mmol/l 131,5±10,1 82,1±8,1 P1-2= 0,001 ASAT, units/l 132,5±6,9 171,0±12,0 P1-2= 0,011 ALAT, unit/l 51,7±2,5 59,03±3,1 P1-2= 0,080 ALP, units/l 150,6±3,0 166,0±6,0 P1-2= 0,032 LDH, units/l 547,0±21,0 669,0±37,0 P1-2= 0,009 TC, mol/l 1,61±0,1 1,5±0,06 P1-2= 0,356 HDL cholesterol, mol/l 1,54±0,06 1,31±0,03 P1-2= 0,003 LDL cholesterol, mol/l 0,28±0,034 0,25±0,04 P1-2= 0,574 VLDL cholesterol, mol/l 0,4±0,025 0,49±0,035 P1-2= 0,049 AI, standard unit 0,045±0,006 0,13±0,04 P1-2= 0,048 TG, mol/l 1,03±0,08 1,2±0,05 P1-2= 0,086 NEFA, mol/l 0,68±0,02 0,83±0,04 P1-2=0,003 Sodium, mmol/l 146,5±0,69 141,4±1,72 P1-2= 0,012 Potassium, mmol/l 6,09±0,25 5,26±0,17 P1-2= 0, 012 Calcium, mmol/l 2,5±0,04 2,3±0,03 P1-2= 0,001 Ferrum, µmol/l 23,5±1,29 19,12±0,39 P1-2= 0,004 Ferritin, µg/l 125±9,34 140±5,68 P1-2= 0,184 Further, the table shows that the intake of small doses of As a result, the Atherogenic Index (AI) in rats of the benzene into the bodies of animals led to an increase in the experimental series was 2.7 times higher than in intact activity of serum enzymes, while the activity of ASAT in the animals.
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